System for determining peripheral artery disease and method of use

ABSTRACT

A system for determining peripheral artery disease and method of use for determining the presence or absence of peripheral vascular disease and the severity of the disease in particular vascular segments. The System for determining peripheral artery disease and method of use includes a continuous wave Doppler transceiver which generates a digitized version of quadrature detected stereo audio and is coupleable to a waveform converter and processor. The waveform converter and processor provides filtering, time domain to frequency domain conversion, gain control, and statistical processing of the converted Doppler Stereo audio and is operationally coupled to a display for presenting results to a technician.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. Provisional Application No.62/257,191 filed on Nov. 18, 2015, entitled System for DeterminingPeripheral Artery Disease and Method of Use, which is incorporatedherein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

JOINT RESEARCH AGREEMENT

Not Applicable

STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINTINVENTOR

Not Applicable

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to methods for determining peripheralvascular disease and obtaining haemodynamic data and more particularlypertains to a new system for determining the presence or absence ofperipheral vascular disease and the severity of the disease inparticular vascular segments.

Background Information

Haemodynamics (or Hemodynamics) is the fluid dynamics of blood flow. Thecirculatory system is controlled by homeostatic mechanisms, much ashydraulic circuits are controlled by control systems. Haemodynamicresponse continuously monitors and adjusts to conditions in the body andits environment. Thus haemodynamics explains the physical laws thatgovern the flow of blood in the blood vessels. The relationships can bechallenging because blood vessels are complex, with many ways for bloodto enter and exit under changing conditions.

The heart is the driver of the circulatory system, pumping blood throughrhythmic contraction and relaxation. The rate of blood flow out of theheart (often expressed in L/min) is known as the cardiac output (CO).

Blood being pumped out of the heart first enters the aorta, the largestartery of the body. It then proceeds to divide into smaller and smallerarteries, then into arterioles, and eventually capillaries, where oxygentransfer occurs. The capillaries connect to venules, and the blood thentravels back through the network of veins to the right heart. Themicro-circulation—the arterioles, capillaries, and venules—constitutesmost of the area of the vascular system and is the site of the transferof O₂, glucose, and enzyme substrates into the cells. The venous systemreturns the de-oxygenated blood to the right heart where it is pumpedinto the lungs to become oxygenated and CO₂ and other gaseous wastesexchanged and expelled during breathing. Blood then returns to the leftside of the heart where it begins the process again.

In a normal circulatory system, the volume of blood returning to theheart each minute is approximately equal to the volume that is pumpedout each minute (the cardiac output). Because of this, the velocity ofblood flow across each level of the circulatory system is primarilydetermined by the total cross-sectional area of that level. This ismathematically expressed by the following equation:v=Q/A

where

v=velocity (cm/s)

Q=blood flow (ml/s)

A=cross sectional area (cm²)

The blood pressure in the circulation is principally due to the pumpingaction of the heart. The pumping action of the heart generates pulsatileblood flow, which is conducted into the arteries, across themicro-circulation and eventually, back via the venous system to theheart. During each heartbeat, systemic arterial blood pressure variesbetween a maximum (systolic) and a minimum (diastolic) pressure. Inphysiology these are often simplified into one value, the mean arterialpressure (MAP), which is calculated as follows:MAP≈⅔(BP_(dia))+⅓(BP_(sys))

Note: BP_(dia) weighted more heavily since the heart spends two thirdsof the heart beat cycle in the diastolic.

where:

MAP=Mean Arterial Pressure

BP_(dia)=Diastolic blood pressure

BP_(sys)=Systolic blood pressure

A stenosis is an abnormal narrowing of a blood vessel. A stenosis may becaused by atherosclerosis, diabetes, ischemia, calcification, infection,birth defects, or smoking. An occlusion is a blockage of a blood vessel.Either a stenosis or an occlusion affects the ability of a blood vesselto allow blood flow and may restrict or block blood flow.

With human life expectancy increasing worldwide the effects ofprogressive arterial disease become more apparent within the ageingpopulation. This disease commonly takes the form of stenosis (localizedcross sectional arterial narrowing) which may represent a significantresistance to blood flow in, for instance, the iliac, femoral,popliteal, peroneal, tibial, and pedal arteries resulting inclaudication or critical limb ischemia. The effect of a stenosis onresistance is nonlinear, causing symptoms when narrowing exceeds athreshold value.

Where narrowing completely obscures the arterial cross section thestenosis becomes an occlusion. In this case smaller calibre arteries(collateral) direct blood flow past the occlusion, often rejoining theoriginal arterial pathway downstream of the occlusion. In effect thecollateral pathway can be modelled as a special case of a stenosis. Itshould be noted that collateral flow also starts to develop around astenosis as the lumen becomes more obscured. In what follows a stenosisor an occlusion will be used interchangeably where permitted by thecontext and will be referred to collectively as ‘disease’ or ‘a lesion’.

In order to gauge the clinical significance of individual lesions, localhaemodynamic information needs to be obtained.

Ultrasound based Doppler shift spectral analysis and imaging techniquesusing Continuous Wave Doppler and Duplex scanning machines allowvelocity and (in the latter case) flow rate data to be directly measurednon-invasively in many accessible parts of the vascular network.Similarly, techniques exist for calculating blood velocity and flowrates from Magnetic Resonant Imaging (MRI) data (see ‘Real-timevolumetric flow measurements with complex-difference MRI’ Thompson R Band McVeigh E R in Magnetic Resonance in Medicine Vol 50, Issue 6, Pages1248-1255, herewith incorporated by reference herein). MRI data can beobtained from all parts of the vascular network, some of which areinaccessible to ultrasound scanners.

DESCRIPTION OF THE PRIOR ART

The use of both invasive and non-invasive techniques to determine theexistence and extend of peripheral vascular disease (peripheral arterialdisease; progressive arterial disease, PAD, artheriosclerosisobliterans, and similar conditions (collectively referred to herein asPAD) is known in the prior art. Additionally, techniques for measuringlocal mean blood pressure from velocity or flow rate waveforms and theirapplication to detecting stenosis is also known. As an illustrativeexample refer to United States Patent Application publication US2012/0123246 A1 published on May 17, 2012 to King et. al. which ishereby incorporated by reference.

PAD may first show its effects in the legs and feet. The narrowing ofthe arteries may progress to total closure (occlusion) of the vessel.The vessel walls become less elastic and cannot dilate fully or at allto allow greater blood flow when needed, such as during exercise. Thisis a common disorder, which can affect anyone, but often affects menover 50 years old. PAD is one of the fastest growing disease processesin the world and may affect over 200 million people worldwide. PAD hasbeen estimated to affect 12% to 14% of the general population. Themajority of patients are asymptomatic (do not show symptoms) and areundiagnosed. For patients with symptoms, the symptoms often affect onelimb and may present as leg pain (intermittent claudication) which maybe aggravated by exercise and relieved with rest; numbness of the legsor feet at rest; cold legs or feet, muscle pain in the thighs, calves,or feet; change of color of the legs; paleness or blueness (cyanosis), aweak or absent pulse in the limb, or walking/gait abnormalities.However, it has been estimated that approximately one-third of patientswith symptoms of PAD do not report them to their doctor. As a result ofboth asymptomatic and unreported cases, a high risk group of patientsare under diagnosed and receive either no treatment or sub-optimaltreatment.

There are several currently utilized modalities used for diagnosing PAD.PAD may be revealed by an abnormal ratio between the blood pressure ofthe ankle and arm (ankle/brachial index or ABI). A decrease in bloodpressure from the brachial artery (close to the bicep in the upper arm)to the ankle would suggest a stenosis (narrowing) or an occlusion(blockage) in the arteries somewhere between the Aorta and the ankle.

The test for determining ABI may be performed with a sphygmomanometer(blood pressure cuff and gauge) and a stethoscope or continuous waveDoppler ultrasonic probe for detecting the sound waves associated withthe blood flow. The systolic pressure may be determined for eachlocation and compared in the form of a ratio. This test may be performedin a physician's office, laboratory, or even in the field. However, themedical personnel performing this test must have a basic knowledge ofarterial anatomy and must be trained in how to perform the ABI testingsuch that valid and repeatable reading may be obtained. Thus, while itis not necessary to have a physician perform the test, skilled personnelare generally required.

Historically, ankle/brachial pressure index (ABPI) has been used as aconvenient indicator of clinically significant peripheral arterialdisease in the lower limbs. Systolic pressure can be simply obtained byplacing a CW Doppler device over the artery immediately downstream of anencompassing pressure cuff. When the cuff is inflated to equal or justexceeds the systolic blood pressure within the artery, the audio signalfrom the Doppler device will cease. By recording the cuff pressure atthat precise moment, the intra-arterial systolic pressure is assumed tobe equal the cuff pressure. An arm and an ankle blood pressure cuff areapplied. In the presence of one or more clinically significant lesionswithin the arteries supplying the lower limbs, the ratio betweenankle/arm systolic pressures falls below a pre-established thresholdvalue. This measurement is typically carried out on a rested, supinesubject.

While ABI is currently used to diagnose PAD, it is not accurate incalcified diabetic lesions (stenosis or occlusions), which may make upmore that 30% of all PAD patients. It does not work because calcifiedlesions are incompressible causing an artificially high pressure readingin the ankle and a falsely elevated ABI. Additionally it is challengingto perform properly in chair bound patients, and is often too painfulfor patients with foot or ankle wounds. The cuff may be painful orintroduce infection to their wounds.

In some instances, ABI is used with duplex and/or Doppler waveforms totry to overcome these limitations. However, in such cases, generallyvascular surgeons and/or radiologists are required to interpret theresults, which significantly increases the cost, and limits theavailability of meaningful detection.

Distally the circulatory system consists of a series of arterialbifurcations. The characteristic resting blood flow waveforms in themajor transit blood vessels are dominated by constructive interferencebetween flow waves reflected from the periphery and re-reflected fromthe bifurcation. This results in a distinctive notch (a change in slopedirection from negative to positive that occurs during diastole afterthe dicrotic notch) in the flow waveform shape within disease freearterial system, referred to herein as a ‘C-notch’. In the presence ofproximal disease the constructive interference changes to destructiveinterference, effectively eliminating the C-notch.

In these respects, the System for determining peripheral artery diseaseand method of use according to the present invention substantiallydeparts from the conventional concepts and designs of the prior art, andin so doing provides an apparatus primarily developed for the purpose ofproviding a clear indication of the presence or absence of PAD andsignificantly reducing the amount of training necessary to reliably andrepeatablly perform the diagnostic test.

SUMMARY OF THE INVENTION

In view of the foregoing disadvantages inherent in the known types ofhaemodynamic measurement and monitoring systems and methods now presentin the prior art, the present invention provides a new System ForDetermining Peripheral Artery Disease and Method of Use wherein the samecan be utilized for analyzing a Doppler waveform providing a clearindication of the presence or absence of PAD and significantly reducingthe amount of training necessary to perform the diagnostic test in arepeatable and reliable manner.

To attain this, the present invention generally comprises a Dopplertransceiver, a waveform converter and processor, and a display fromproviding a visual result for the user.

Various embodiments and implementations of the present invention will beprovided. It is important to note that a limitation described in oneembodiment or implementation is not necessarily a limitation for anyother embodiment or implementation unless specifically described assuch.

In an embodiment, the person performing the testing using the presentinvention (referred to as a “technician” without regard to the degree ofskill or training of any particular user) will use the continuous waveDoppler transceiver to obtain stereo audio of the blood flow through thevessels of concern, such as a femoral, popliteal, peroneal, anteriortibial, posterior tibial or pedal artery. It is important to note, thatwhile the present invention has significant applicability as areplacement for a traditional ABI test, it also has broaderapplicability for testing other arterial structures and fistuals. Also,it is important to note that the technician obtains the stereo audio ofthe blood flow in the vascular segment of interest without the need of apressure cuff allowing for greater applicability including patients in aseated position, those with open wounds, and those with significantcalcification which may result in limited compressibility orincompressibility of the blood vessel of interest.

In a further embodiment, the continuous wave Doppler transceiver iswireless. In such an embodiment, the continuous wave Doppler transceivertransmits the audio information to the waveform converter and processor.Those skilled in the art will recognize that the format of the audioinformation may take on many forms without departing from the spirit ofthe present invention. It is preferred however that the audioinformation is digitized at this stage to improve transmissioncharacteristics and performance, and to reduce the likelihood ofinterference during transmission.

In a further preferred embodiment, the Doppler stereo audio produced bythe wireless Doppler transceiver is the baseband converted version ofthe Doppler-shift signals received back from moving blood, This isproduced within the wireless Doppler transceiver by quadraturedetection, allowing for the directionality of movement to be preserved(towards versus away from the transducer).

In still a further embodiment, the waveform converter and processorreceives a digitized version of the stereo audio of the blood flow andprocesses the signal to reduce artifacts.

The waveform converter and processor is a physical device which providesfiltering, time domain to frequency domain conversion, gain control, andstatistical processing of the converted Doppler Stereo audio. This maybe implemented as an all hardware solution, or as a hardware devicewhich implements specific functions through software controlledprocessors. It should also be understood that for at least the purposesof this illustrative embodiment, that the waveform converter andprocessor is operationally coupled to a “real time” visual display ofthe Doppler Stereo Audio and audio itself is provided to aid theoperator in finding the appropriate blood vessel and maximizing thesignal received.

In at least one embodiment, the processing typically includes, but maynot be limited to:

-   -   (a) taking a short time series of audio samples;    -   (b) weighting the data to limit “end effects” of sampling;    -   (c) performing a Complex Fast Fourier Transform;    -   (d) taking the moduli of the frequency values; and    -   (e) unscrambling the amplitude values to represent forward and        reverse signal.

The system described broadly herein aids the operator in identifying thepresence of a C-notch that they would not be able to identify in anaccurate and repeatable manner without the use of the describedinvention. It aids the operator in several ways including eliminatingvariability in the analyzed data that results from operator or patientmovement, only accepting data that is representative of physiologicallyaccurate waveforms, ignoring data where a dicrotic notch is present, andidentifying significant disease by identifying a lack of features in thewaveform that result from summing reflected waves in healthy patients.

There has thus been outlined, rather broadly, several important featuresof the invention in order that the detailed description thereof thatfollows may be better understood, and in order that the presentcontribution to the art may be better appreciated. There are additionalfeatures of the invention that will be described hereinafter and whichwill form the subject matter of the claims appended hereto.

In this respect, before explaining at least one embodiment of theinvention in detail, it is to be understood that the invention is notlimited in its application to the details of construction and to thearrangements of the components set forth in the following description orillustrated in the drawings. The invention is capable of otherembodiments and of being practiced and carried out in various ways.Also, it is to be understood that the phraseology and terminologyemployed herein are for the purpose of description and should not beregarded as limiting.

As such, those skilled in the art will appreciate that the conception,upon which this disclosure is based, may readily be utilized as a basisfor the designing of other structures, methods and systems for carryingout the several purposes of the present invention. It is important,therefore, that the claims be regarded as including such equivalentconstructions insofar as they do not depart from the spirit and scope ofthe present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood and objects of the inventionwill become apparent when consideration is given to the followingdetailed description thereof. Such description makes reference to theannexed drawings wherein:

FIG. 1 is a schematic functional block diagram representation of anembodiment of the present invention.

FIG. 2 is a schematic diagram of an illustrative waveform with a C-Notchof a nominal healthy patient.

FIG. 3 is a schematic diagram of an illustrative waveform indicatingserious disease.

FIG. 4 is a schematic diagram of an embodiment of the present inventionin use.

DESCRIPTION OF PREFERRED EMBODIMENTS

With reference now to the drawings, and in particular to FIGS. 1 through4 thereof, a new System For Determining Peripheral Artery Disease andMethod of Use embodying the principles and concepts of the presentinvention and generally designated by the reference numeral 10 will bedescribed

With the preceding general description of the system of the presentinvention as background, we now address the specific advantages of thepresent invention in being able to present not only an improved solutionfor providing a clear indication of the presence or absence of PAD tothe technician and other diagnostic improvements as discussed below.

The present invention is able to detect a ‘C-notch’ in the convertedDoppler stereo audio which is indicative of the presence or absence ofPAD.

As described above the present invention 10 incorporates a waveformconverter and processor 20, which in part converts the Doppler stereoaudio into a frequency domain (velocity flow) representation which canbe presented to the technician through the display. Traditional Dopplerwaveform analysis when compared to invasive angiography has providedinsights into “normal” waveforms as well as changes in these waveformscaused by various degrees of stenosis or occlusion. A discussion ofthese waveforms in included in Monotonic Doppler Ultrasound SpectralWaveforms in Peripheral Arterial Disease by Dr. M. Al-Qaisi, Thesis forthe Degree of Doctor of Medicine (M.D.), University of London, 2010(“Al-Qaisi Thesis”), which is hereby incorporated by reference.

The Al-Qaisi Thesis also includes a detailed discussion of the potentialapplicability of Monotonic waveforms, specifically their presence orabsence, as a detection of significant arterial disease. A monotonicwaveform is defined as one that does not include the C-notch. Anon-monotonic waveform does include the C-notch. The present inventionbuild on this foundation and provides significant improvement byproviding a statistical analysis of Doppler waveforms to provide astandalone indication of presence or absence of significant diseasewithout requiring highly skilled individuals to provide aninterpretation of the Doppler waveforms.

FIG. 2 shows various aspects of a waveform which includes the C-notchincluding; (a)—designation of the C-notch; (b)—the waveform; (c) thesystolic peak; (d) the negative peak, (e) the time from the systolicpeak to the secondary peak, and (f) the time of a single cardiac cycle.

FIG. 3 shows the (g)—systolic peak and (h) the time of a single cardiaccycle for a waveform which does not include the notch for a patienthaving significant disease.

In at least one preferred embodiment, the Doppler transceiver 20 isuniquely paired with the waveform converter and processor 30 to limitinterference from other units and to enhance data security.

The basic functionality of the waveform converter and processor 30 shallbe described in the next several paragraphs. While the waveformconverter and processor 30 may be implemented in an all hardwareconfiguration or in a hardware configuration which utilizes softwarecontrolled processors, the following description may include terms ofart typical of software implementations for purposes of clarity, butsuch terminology should not be read as requiring a softwareimplementation.

The waveform converter and processor 30 receives the Doppler stereoaudio data from the Doppler transceiver 20 and then spectrally analyzesthe signal to produce a directional sonogram (which may be displayed),determine the maximum frequency outline in both directions, and finallygenerate from these outlines various numerical parameters and clinicalindicators.

In at least one preferred embodiment, the waveform converter andprocessor 30 performs functions including:

-   -   Taking a short time series of audio samples (128×2 data values);    -   Weighting the data to limit ‘end effects’ of sampling (Hanning        Weighting);    -   Performing a Complex Fast Fourier Transform (128*2 frequency        values);    -   Taking the moduli of the frequency values (128 amplitude        values);    -   Unscrambling the amplitude values to represent forward and        reverse signal. AF0-AF63 unchanged, AF64-AF127 become        AF-64-AF-1; and    -   Setting amplitude AF0 to zero.

Dependent of the data sampling rate, a form of ‘sliding transform’ isimplemented in order to maintain a standard sonogram display with a timedisplay resolution of 10 ms. Display frequency ranges of +/−8 kHz, +/−4kHz or +/−2.5 kHz are provided to cover the range of signals foundclinically.

The sliding transform process allows a full 128 data point FFT to beperformed every 10 ms, whether or not 128 new data samples have actuallybeen created within this time period. An appropriate number of oldsamples may be used along with the newly available samples to make upthe total of 128.

RANGE SAMPLE RATE SAMPLES/10 mS REUSED +/−8 kHz 16 ksps 160 0 +/−4 kHz 8ksps 80 48 +/−2.5 kHz 8 ksps 50 78

This process results in a common data output rate independent of displayfrequency range, and gives a practical time and frequency resolution of˜1% for clinical blood flow signals

Since the 1970s, the maximum frequency outline of the Doppler spectraldisplay has been used as the most significant feature of the sonogram,and shown to be clinically indicative of health and disease.

The present invention determines the outline, based on the full datawithin each vertical spectral line and also that of nearby lines.Forward and reverse data are treated separately.

For each direction of flow, the amplitudes are accumulated through thewhole frequency range from F1 to F63, (ignoring any amplitude below asmall threshold). The total is divided by 16, and then a subtractionprocess is performed on the total/16, from F63 down to F1, stopping whenthe accumulator reaches zero. This gives a ‘15/16 MaxF’. The result isthen scaled back up by multiplying the result by 16/15.

As most Doppler flow signals have the form of ‘bounded white noise’ withsome additional background noise, this has been found to produce a goodequivalent to manual waveform outlining.

Further processing smooths the outline in time—to limit the short termoutline variations, given that the underlying audio signal is stochasticin nature.

In a further embodiment, median filtering is used to reduce the effectof sudden drops/spikes in individual spectral sweeps. The MaxF for agiven point in time is replaced by the median value of the MaxF from t−2to t+2 (a 5 point median)

In still a further embodiment, this is then further smoothed by using asimple 5 point smoothing algorithm on the median'd data, each MaxF beingthe average of its adjacent points (t−2 to t+2).

While this can smooth out sharp dips/bumps in the MaxF outline, itprovides a more statistically reliable value and minimizes drop-outs andspikes caused when the gain is low or that are caused by operator handor patient movement.

Preferably, the waveform converter and processor 30 superimposes theMaxF and MinF outlines on the sonogram in real-time to assist theoperator in setting the appropriate gain and identifying any interferingsignals.

Deriving Parameters and Features from the Sonogram Outlines

At the end of each four second sonogram sweep, the updating of thesonogram pauses and the MaxF/MinF data is interrogated. If the data isdetermined as satisfactory, the derived values are presented on thedisplay 40. Otherwise further sonogram data is gathered until such timeas valid data is detected.

In at least one embodiment, an option to average the spectral data maybe used if the individual 4 second sonograms fail to provide valid datapromptly. This takes four screens worth of sonogram and superimposes thedata from all recognized cardiac cycles to produce one ‘ensembleaverage’ cycle. This average is then displayed and reanalyzed. Thisrarely fails to obtain a result.

Identifying Individual Cardiac Cycles

As the systolic upswing in the Doppler flow data is the single mostsignificant and reliable indicator of the cardiac cycle, the process ofidentifying these is performed by identifying the maximum height of theMaxF outline across the whole 4 seconds of data (bigpeak).

The gradient of the forward MaxF waveform across the 4 seconds isdetermined, and then each local minimum is found together with its firstfollowing maximum. This produces a table of peaks being possible cardiaccycle starts.

If at least two ‘peaks’ are found, the data is checked and accepted as‘possible’ systolic peaks if each identified ‘peak’ is at least 75% ofthe ‘bigpeak’ and the difference in height from foot to peak is greaterthan 3/64.

Finally, short cardiac cycles are rejected if peak-peak time is lessthan 400 ms (40 sweeps). A resultant table of ‘goodpulses’ results,containing both heights and positions of each accepted cardiac cyclestart (foot), systolic peak and any further small positive peaks.

Monotonicity Detection

The present inventions uses monotonicity detection as an indication ofarterial disease. Monotonicity is defined here as: the absence of anypeak in MaxF outline between the forward systolic peak and end diastole(the foot of the following waveform) when forward flow exists,throughout the cardiac cycle (height of next foot >0), and no reverseflow peaks exist.

The first requirement is to detect any post-systolic upswing, which isdone by searching across the cardiac cycle data already tabulated, fromsystolic peak to next foot, noting the first detected upswing which hasa rise of greater than 1/20 the size of the cycle's own systolicfoot-to-peak amplitude, whilst not reaching a maximum value greater than70% of its associated systolic peak.

This has been found to avoid false detection due to remaining stochasticvariations in MaxF and due to drop-out or mis-identification of systolicpeaks.

The position of each foot, systolic peak and second positive peak (ifpresent) are superimposed as vertical lines on the frozen sonogram.

Before conclusive decisions are made, the reverse flow MinF data isprocessed to identify any negative flow peaks.

All negative peaks which rise from zero to a maximum greater than 2/64are identified in the MinF data.

For each direction of flow, the amplitudes are accumulated through thewhole frequency range from F1 to F63, (ignoring any amplitude below asmall threshold). The total is divided by 16, and then a subtractionprocess is performed on the total/16, from F63 down to F1, stopping whenthe accumulator reaches zero. This gives a ‘15/16 MaxF’. The result isthen scaled back up by multiplying the result by 16/15.

Acceptable negative peaks are limited to those which start after theforward systolic peak and within 300 ms of it. The first acceptablenegative peak found is marked on the frozen sonogram.

As nearby venous (reverse flow) is often an interfering signal whenobserving arterial flow, the requirement for real arterial reverse flowto start only after peak systole helps to eliminate such interference.It also helps to prevent wall-thump interference which occurs only atsystolic upswing. A first negative peak starting more than 300 ms afterthe positive peak is not likely to be as a result of local haemodynamicstate (may be caused by cardiac regurgitation).

Finally, the waveform is determined to be monotonic if there are noidentified positive or negative secondary peaks (notches) and the enddiastolic flow is positive. If however at least one forward or reversenotch is detected, the waveform is determined to be non-monotonic.Alternately, if no notches are detected and there is no end diastolicflow, no determination can be made.

The conversion and processing is now complete and the indication of thepresence or absence of monotonicity and displayed on the visual displayfor use by the technician.

If accepted, all relevant data may be stored to disc or other suitablemedia.

Ensemble Average

Where poor quality, noisy, or low velocity signals are found, thepresent invention may perform an ‘ensemble average’ of four screens (16seconds) of data to produce one clearer, more definite, andstatistically relevant waveform for analysis. Once four screens-full ofvalid data have been obtained, the process of ensemble averaging begins.The longest foot-systolic peak is found amongst all identified cycles.The shortest systolic peak to next foot is similarly found. For eachidentified systolic peak, a section of sonogram is copied (Systolic peaktime—longest foot) to (Systolic peak time+shortest next). These copiesare ‘superimposed’, automatically aligning the data with respect to thesystolic peaks (all pixel values summed individually across allidentified waveforms then normalized by number summed). This compositewaveform is written repeatedly across a 4 second sonogram and displayed.Finally the composite sonogram is subjected to full analysis as thoughit had been one 4 second sweep, and the results shown.

Supporting Study

In order to establish the accuracy of the present invention inseparating significant from non-significant lower limb occlusivedisease, a study was conducted, the results of which are describedbelow.

Objectives

Establish the present invention's accuracy in separating significantfrom non-significant lower limb occlusive disease using Color Duplex asan acceptable modern ‘gold standard’.

Examine the distribution of perfusion pressure and ‘cuff free ABI’ inthe significant and non-significant disease groups.

Methods

The study adhered to the provisions of the Declaration of Helsinki. Itinvolved 225 limbs of patients who presented to the vascular lab withsymptoms consistent with peripheral artery disease. There were noexclusion criteria. Patient mix included diabetics, claudicants andischaemic limbs. Symptoms included rest pain, swelling legs andulcerated extremities. Patients were first tested for significant ornon-significant occlusive arterial disease with the present invention.This involves taking an arm BP and acquiring Doppler spectra from theposterior or anterior tibial artery. The present invention automaticallyidentifies the presence of the ‘notch’ feature which characterizes limbswith none or non-significant arterial disease. A real time statisticalanalysis rejects ‘non physiological’ waveforms, then automaticallycalculates ‘cuff free ABI’, pedal perfusion pressure and vascularreserve when a minimum of two successive ‘valid’ waveforms areidentified. The patient was then immediately assessed by Color Duplex.Significant occlusive arterial disease criteria ranged from completeocclusion down to and including 50% stenosis (as indicated by a peaksystolic velocity ratio of 4 or greater

Results

Of the 225 limbs evaluated, 119 of them were determined to not havesignificant disease and 106 were determined to have significant disease.

There were 205 limbs that had a diagnosis that was consistent with theduplex control [true positive]. Three of the patients who were exercisedhad a false diagnosis that became true after exercise. All three wereconfirmed by duplex. About 3.1% of the limbs gave an equivocal resultand 1.3% of the limbs had an unreadable waveform.

This shows the present invention has a sensitivity of 95.1%, aspecificity of 98.2%, and an accuracy of 96.8%. There is less than a 1%false positive rate and a 2.2% false negative rate assuming Duplex is100 percent correct. (Table 1)

TABLE 1 Outcomes of 225 limbs evaluated by the present invention. [119negative assessments and 106 positive assessments according to duplex.Positive assessment is defined as >50% stenosis] number true true falsefalse unreadable of limbs positive negative positive negative equivocalwaveform 225 98 110 2 5 7 3

TABLE 2 Sensitivity, specificity, and accuracy of the present inventionin 225 limbs as compared to plain old ABI and Duplex from theliterature. Plain old ABI* Present Invention Sensitivity 77% 95.10%Specificity 74% 98.20% Accuracy 76% 96.80% *Data taken from Allen, Oateset al ‘Comparison of Lower Limb Arterial Assessments Using Color-DuplexUltrasound and Ankle/Brachial Pressure Index Measurements’, Angiology1996 47: 225, DOI: 10.1177/000331979604700302

The distribution of ‘Cuff free’ ABI values vs Duplex demonstratedsignificant/no significant disease evaluation was analyzed. A simpleGaussian distribution was assumed. The following values were obtained:

None or no significant disease on Duplex scan: ABI meanvalue=0.894+/−0.076 Significant disease on Duplex scan: ABI meanvalue=0.614+/−0.137.

It can be seen that the crossover point for the two groups isapproximately at the 1 Standard Deviation level (0.75). This isconsistent with the lower theoretical maximum value of 1.0 for the ‘cufffree’ method.

In the true positive group 53.8% of the patients had a vascular reserveof above 15% and the 46.2% of the patients had a vascular reserve ofless than 15%. In the true negative group all of the patients had avascular reserve of greater than 15%. (Table 3)

TABLE 3 Number of limbs with VR <15% after a true positive and truenegative assessment Vascular Reserve (%) True positive Truenegative >0.15 50 (53.8%) 108 (100%) <0.15 43 (46.2%) 0 (0%)

Of the patients with a true positive outcome 69.2% had a mean perfusionpressure of greater than 40 mmHg and 30.8% of the patients had a meanperfusion pressure of less than 40 mmHg. In the true negative group 99%of the patients had a mean perfusion pressure of greater than 40 mmHgand only 1% of the patients had a mean perfusion pressure of less than40 mmHg. (Table 4)

TABLE 4 Number of limbs with mean perfusion pressure <40 mmHg after atrue positive and true negative assessment mean perfusion pressure truepositive true negative >40 mmHg 36 (69.2%) 102 (99%) <40 mmHg 16 (30.8%)1 (1%)

The results from the supporting study demonstrate that the presentinvention has a sensitivity of 95.1%, a specificity of 98.2%, and anaccuracy of 96.8%. There is less than a 1% false positive rate and a2.2% false negative rate assuming Duplex is 100 percent correct.

Further advantages of the invention, along with the various features ofnovelty which characterize the invention, are pointed out withparticularity in the claims annexed to and forming a part of thisdisclosure. For a better understanding of the invention, its operatingadvantages and the specific objects attained by its uses, referenceshould be made to the accompanying drawings and descriptive matter inwhich there are illustrated preferred embodiments of the invention.

Additionally, as those skilled in the art will readily recognize, theindividual thresholds, timing metrics, filtering criteria, and othersimilar values stated above may be adjusted, expanded, or condensed aspart of an overall implementation strategy without departing form thescope of the present invention.

Index of Elements for System for determining peripheral artery diseaseand method of use □    □    □    □    □    □    □    □    □    □    □10. System for determining peripheral artery disease and method of use □11. □ 12. □ 13. □ 14. □ 15. □ 16. □ 17. □ 18. □ 19. □ 20. DopplerTransceiver □ 21. □ 22. □ 23. □ 24. □ 25. □ 26. □ 27. □ 28. □ 29. □ 30.Waveform Converter and Processor □ 31. □ 32. □ 33. □ 34. □ 35. □ 36. □37. □ 38. □ 39. □ 40. Display □ 41. □ 42. □ 43. □ 44. □ 45. □ 46. □ 47.□ 48. □ 49. □ 50. □ 51. □ 52. □ 53. □ 54. □ 55. □ 56. □ 57. □ 58. □ 59.□ 60. □ 61. □ 62. □ 63. □ 64. □ 65. □ 66. □ 67. □ 68. □ 69. □ 70. □ 71.□ 72. □ 73. □ 74. □ 75. □ 76. □ 77. □ 78. □ 79.

We claim:
 1. A system for determining peripheral artery diseasecomprising: a Doppler transceiver for capturing an audio representationof blood flow through a blood vessel of interest, wherein the Dopplertransceiver is a continuous wave Doppler transceiver which produces abaseband stereo audio representation of Doppler-shift signals receivedback from moving blood by quadrature detection preserving directionalityof blood flow; a waveform converter and processor coupled to the Dopplertransceiver, wherein the Doppler transceiver digitizes the basebandstereo representation into a digitized baseband stereo representationand transmits the digitized baseband stereo representation to thewaveform converter and processor, and wherein the waveform converter andprocessor is further configured to: receive the digitized basebandstereo representation, capture a series of short time samples, andprovide initial filtering of the samples, convert the series of shorttime samples into a frequency domain representation of the basebandstereo audio representation of Doppler-shift signals, provide spectralanalysis of the frequency domain representation to produce a directionalsonogram, detect a presence or an absence of any peaks in thedirectional sonogram between a forward systolic peak and an end diastolefor a cardiac cycle, and generate a monotonicity detection if asecondary peak or a reverse flow secondary peak is not identified and adiastolic flow at the end of the cardiac cycle is positive; and adisplay coupled to the waveform converter and processor for providingvisual indicia for a user, wherein the visual indicia includes agraphical representation of the directional sonogram, positionalindications of features of the directional sonogram, and a monotonicityindicator based on the monotonicity detection.
 2. The system of claim 1,wherein the Doppler transceiver captures the audio representation ofblood flow via waveforms in the blood vessel of interest, arising fromreflections generated by a periphery bifurcation and a proximalbifurcation.
 3. The system of claim 2, wherein the Doppler transceiverdigitizes the audio representation for transmission to the waveformconverter and processor.
 4. The system of claim 3, wherein a C-notch, isdetected.
 5. The system of claim 4, wherein the Doppler transceiver iswirelessly coupled to the waveform converter and processor.
 6. Thesystem of claim 5, wherein the Doppler transceiver is uniquely paired tothe waveform converter and processor.
 7. The system of claim 1, whereinthe waveform converter and processor generates a maximum frequencyoutline for both forward and reverse blood flow.
 8. The system of claim1, wherein the waveform converter and processor filters and detects asecondary peak that has an amplitude between 5% and 70% of the amplitudeof the forward systolic peak of the cardiac cycle.
 9. The system ofclaim 1, wherein the waveform converter and processor filters anddetects a secondary peak that has an amplitude between 2% and 85% of theamplitude of the forward systolic peak of the cardiac cycle.
 10. Thesystem of claim 9, wherein the waveform converter and processor filtersand detects a reverse flow secondary peak greater than 2/64th of amaximum reverse flow peak.
 11. The system of claim 10, wherein anupswing of less than 5% of a foot to peak amplitude of the cardiac cycleis rejected to avoid false negatives from detection of a dicrotic notch.12. The system of claim 10, wherein an upswing of less than 15% of afoot to peak amplitude of the cardiac cycle is rejected to avoid falsenegatives from detection of a dicrotic notch.
 13. The system of claim10, further comprising: identifying an upswing in a given cardiac cyclethat is greater than 70% of the forward systolic peak.
 14. The system ofclaim 10, further comprising: identifying an upswing in a given cardiaccycle that is greater than 60% of the forward systolic peak.
 15. Thesystem of claim 10, wherein a negative peak is accepted if the negativepeak is after a start of the forward systolic peak and less than 300milliseconds after a start of the cardiac cycle.
 16. The system of claim10, wherein a negative peak is accepted if the negative peak is after astart of the forward systolic peak and less than 400 milliseconds aftera start of the cardiac cycle.
 17. The system of claim 10, wherein anegative peak is accepted if is the negative peak is after a start theforward systolic peak and less than 500 milliseconds after a start ofthe cardiac cycle.
 18. The system of claim 10, wherein a reverse flowdata is accepted after the systolic peak to eliminate interference fromnearby venous flow and from a wall thump in systolic upswing.
 19. Thesystem of claim 10, wherein a standard deviation of time between thepositive systolic peak and a negative peak is calculated from 3 cardiaccycles to determine if a reverse flow data is valid.
 20. The system ofclaim 10, wherein the monotonicity indicator is set to determine if aforward foot peak time percentage standard deviation is greater than25%.
 21. The system of claim 10, wherein the monotonicity indicator isset to determine if a forward foot peak time percentage standarddeviation is greater than 15%.
 22. The system of claim 10, wherein themonotonicity indicator is set to determine if a forward foot systolicpeak height percentage standard deviation is greater than 25%.
 23. Thesystem of claim 10, wherein the monotonicity indicator is set todetermine if a forward foot systolic peak height percentage standarddeviation is greater than 15%.
 24. The system of claim 10, wherein themonotonicity indicator is set to determine if a forward foot systolicpeak height percentage standard deviation is greater than 35%.
 25. Thesystem of claim 10, wherein the monotonicity indicator is set todetermine if a forward secondary peak height has a percentage standarddeviation of greater than 25%.
 26. The system of claim 10, wherein themonotonicity indicator is set to determine if a forward secondary peakheight has a percentage standard deviation of greater than 35%.
 27. Thesystem of claim 10, wherein the monotonicity indicator is set todetermine if a forward secondary peak height has a percentage standarddeviation of greater than 20%.
 28. The system of claim 10, wherein themonotonicity indicator is set to determine if a systolic peak tosecondary peak time has a percentage standard deviation of greater than25%.
 29. The system of claim 10, wherein the monotonicity indicator isset to determine if a systolic peak to secondary peak time has apercentage standard deviation of greater than 35%.
 30. The system ofclaim 10, wherein the monotonicity indicator is set to determine if asystolic peak to secondary peak time has a percentage standard deviationof greater than 15%.
 31. The system of claim 10, wherein themonotonicity indicator is set to determine if a negative peak height hasa percentage standard deviation of greater than 25%.
 32. The system ofclaim 10, wherein the monotonicity indicator is set to determine if anegative peak height has a percentage standard deviation of greater than35%.
 33. The system of claim 10, wherein the monotonicity indicator isset to determine if a negative peak height has a percentage standarddeviation of greater than 15%.
 34. The system of claim 10, wherein themonotonicity indicator is set to determine if a cardiac cycle period hasa percentage standard deviation greater than 25%.
 35. The system ofclaim 10, wherein the monotonicity indicator is set to determine if acardiac cycle period has a percentage standard deviation greater than35%.
 36. The system of claim 10, wherein the monotonicity indicator isset to determine if a cardiac cycle period has a percentage standarddeviation greater than 15%.
 37. The system of claim 10, wherein the usercan collect 16 subsequent waveforms and identify a longest foot tosystolic peak, identify a shortest systolic peak to foot is identified,and identified waveforms are superimposed with corresponding time valuesaveraged.
 38. The system of claim 10, wherein the user has an option todisplay a previously stored waveform and data derived from the storedwaveform.
 39. The system of claim 10, wherein a data point is smoothedby taking a median from t−2 to t+2.
 40. The system of claim 10, whereina data point is smoothed by taking an average of the data from t−2 tot+2.
 41. The system of claim 10, wherein minF and maxF outlines aredisplayed in order to assist the user in setting a gain.
 42. The systemof claim 10, wherein 4 scans of waveform data are obtained beforeprocessing.
 43. The system of claim 10, wherein a scan is comprised ofat least 4 sequential cardiac cycles.
 44. The system of claim 10,wherein a start of the cardiac cycle is identified as a maximumfrequency in the cardiac cycle.
 45. The system of claim 10, wherein datafrom a cardiac cycle is rejected if the cardiac cycle time is less than400 milliseconds.
 46. The system of claim 10, wherein data from acardiac cycle is rejected if the cardiac cycle time is less than 600milliseconds.
 47. The system of claim 9, wherein the waveform converterand processor filters and detects a reverse flow secondary peak greaterthan 1/128th of a maximum reverse flow peak.
 48. The system of claim 9,wherein the waveform converter and processor filters and detects areverse flow secondary peak greater than a fraction of a maximum reverseflow peak ranging between 1/28^(th) and 1/16^(th), inclusive.
 49. Thesystem of claim 9, wherein the waveform converter and processor filtersand detects a reverse flow secondary peak greater than a fraction of amaximum reverse flow peak ranging between 1/64^(th) and ⅛^(th),inclusive.
 50. The system of claim 1, wherein a brachial blood pressureis provided by the user as an input for the waveform converter andprocessor.
 51. The system of claim 50, wherein the waveform converterand processor generates a derived parameter descriptive of a blood flowwaveform shape in the blood vessel of interest.
 52. The system of claim51, wherein the derived parameter includes at least one derivedparameter selected from the group consisting of: a Mean ArterialPressure (MAP), a Pressure Pulsality Index, a Flow Pulsality Index, aMean Ankle Brachial Index (ABIm), a Perfusion Pressure, and a VascularReserve.
 53. The system of claim 52, wherein the monotonicity indicatorand derived parameters are presented to a user on the display.
 54. Amethod for determining peripheral artery disease comprising the stepsof: providing the system of claim 21; applying the Doppler transceiverto a peripheral vessel of a patient, wherein the peripheral vessel isselected from the group consisting of a superficial femoral artery(SFA), a popliteal vessel, a peroneal vessel, an anterior tibial vessel,a posterior tibial vessel, or a pedal vessel; determining whether thewaveform presented in the directional sonogram is a monotonic waveform;and indicating a presence or an absence of peripheral artery disease.